rs190192954
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):c.24622G>A(p.Glu8208Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,613,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E8208E) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.24622G>A | p.Glu8208Lys | missense_variant | 85/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.24622G>A | p.Glu8208Lys | missense_variant | 85/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-16020C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152096Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000443 AC: 11AN: 248320Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134684
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461468Hom.: 0 Cov.: 35 AF XY: 0.0000248 AC XY: 18AN XY: 727004
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152214Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74412
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 24, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 01, 2014 | Variant classified as Uncertain Significance - Favor Benign. The Glu6964Lys vari ant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/3868 African American chromosomes by the NHLBI Exom e Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs190192954). Com putational prediction tools and conservation analysis do not provide strong supp ort for or against an impact to the protein, though 1 mammal (bush-tailed rat) c arries a lysine (Lys) at this position raising the possibility that this change may be tolerated. In summary, the clinical significance of the Glu6964Lys varian t is uncertain. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 31, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at